This invention relates generally to devices for use in the surgical repair of heart pathologies, and, more particularly, to antithrombogenic annuloplasty rings which contain relatively rigid biodegradable inserts.
Human heart valves can become deformed or otherwise damaged by any of a number of processes brought on by normal aging and/or disease pathologies. For example, degenerative diseases can cause the valve annulus to become enlarged to the point where the leaflets attached to it cannot fully close. This situation, known as valve incompetence, eventually requires surgical correction by valve repair or replacement procedures. Of the surgical options available for valve reconstruction, valvular annuloplasty represents the procedure most frequently performed, particularly for the tricuspid and mitral valves. Valvular annuloplasty is an operation whereby ring-shaped devices or bands, known as annuloplasty rings, are sewn to the distended valve annulus in order to restore it to its normal, undilated circumference.
Annuloplasty rings are most typically either highly flexible or are stiff and comparatively rigid. Rigid rings typically consists of an open wire element completely covered with cloth. The wire is somewhat stiff yet resiliently deformable and is not intended to be removable from the cloth covering. These annuloplasty rings, because of their rigidity, lie flat and maintain their somewhat oval shape during implantation. Although a rigid ring""s oval shape has been claimed to enhance the competence of the repaired valve, its rigidity can also impede the beneficial flexing movements of the native annulus during the cardiac cycle. Flexible annuloplasty rings generally consist of a soft core of elastomeric material, e.g., silicone rubber, completely enclosed by a sheath of biocompatible cloth. Because of their flexibility, these rings can be difficult to handle during surgical manipulations and generally must be supported during implantation by a holder which is subsequently removed before tying off the implanting sutures.
To overcome some of the deficiencies of flexible and rigid ring structures, an annuloplasty ring would desirably be stiff during handling and implantation, but then become flexible after implantation. As disclosed in U.S. Pat. No. 5,716,397, an annuloplasty ring may consist of a flexible ring into which a rigid structure is inserted to provide temporary rigidity during implantation. Once the ring is implanted and tested, the rigid structure may be removed. However, this approach requires undesirable additional handling after the ring is implanted. Another annuloplasty ring, as disclosed in U.S. Pat. No. 5,104,407, consists of a ring constructed partially of a flexible material and partially of a rigid material. Unfortunately, this ring will be difficult and costly to manufacture and will suffer from the drawbacks afflicting both flexible and rigid rings. In an alternative approach, Chachques et al. (Circulation 82(5), Supplement IV, 82-88, 1990) describes absorbable prosthetic rings for use in pediactric valvular annuloplasty. The rings are reported to address concerns over secondary valvular stenosis in children that can result from implantation of known annuloplasty rings. The rings described by Chachques et al. are synthesized from biodegradable polydioxanone and covered with a porous extensible sewing sheath to allow contact between the polydioxanone, the blood and the endocardium. As a result of this contact, the polydioxanone ring is reported to undergo degradation following implantation.
Many complications associated with the use of implantable medical devices stem from the complex cellular and humoral reactions which occur when a foreign material comes into contact with blood and/or other physiological fluids. Among the most significant of these are the rapid thrombogenic actions which can occur following implantation of a medical device. Initial contact of a device with blood results in deposition of plasma proteins, such as albumin, fibrinogen, immunoglobulin, coagulation factors, and complement proteins. The cellular activities which follow can, among other things, lead to vascular constriction which can hinder blood flow, thrombosis and thrombus accumulation that can result in thromboembolism and stroke, and inflammatory reactions which can damage or impair the function of a medical device.
A variety of methods and compositions have been reported for increasing the thromboresistance of medical device surfaces by bonding or incorporating into or onto the device one or more antithrombogenic agents, such as heparin, hirudin, albumin, phospholipids, streptokinase, tissue plasminogen activator (TPA) or urokinase, hydrophilic polymers such as hyaluronic acid, chitosan, methyl cellulose, and poly(ethylene oxide), poly(vinyl pyrrolidone), growth factors such as endothclial cell growth factor, epithelial growth factor, osteoblast growth factor, fibroblast growth factor, platelet derived growth factor (PDGF), and angiogenic growth factor, and other proteins, carbohydrates and fatty acids.
The present invention is directed to providing annuloplasty rings having antithrombogenic properties which overcome, or at least reducing the effects of, one or more of the problems set forth above.
This invention provides an antithrombogenic annuloplasty ring having sufficient initial rigidity, i.e., prior to implantation, to facilitate ease of handling during surgical manipulations, but which becomes flexible to a desired extent following implantation. The foregoing is accomplished by use of a relatively rigid biodegradable annuloplasty ring insert as a component of an annuloplasty ring. Upon implantation of an annuloplasty ring containing a biodegradable ring insert of this invention, the insert undergoes degradation in the patient""s body as a result of its contact with blood and/or other physiological fluids. The degradation of the biodegradable insert causes a decreasing degree of rigidity of the annuloplasty ring as the insert material is degraded and/or resorbed by the patient""s body.
Therefore, in one aspect of the present invention, there is provided an annuloplasty ring which comprises a biodegradable ring insert and a fabric sheath enclosing the ring insert, wherein the fabric sheath and/or the biodegradable insert have undergone one or more antithrombogenic treatment processes. The ring insert of the annuloplasty ring is at least partly comprised of a biodegradable material selected from any of a variety of biodegradable polymers, including polyanhydrides, polyglycolides, polylactides, polyorthoesters, and other like materials. In one illustrative embodiment, the biodegradable insert is comprised of a highly cross-linked polyanhydride material, particularly one that is photopolymerizable, such as that produced by the photopolymerization of methacrylate anhydride monomers. The fabric sheath which encloses the biodegradable insert, or the biodegradable insert itself, are preferably treated either before, after, or simultaneous with the fabrication of the annuloplasty ring in a manner which causes the incorporation of one or more antithrombogenic agents into or onto the device. The biodegradable insert may further comprise, in addition to the biodegradable materials mentioned above, one or more other components, e.g., plasticizers, stabilizers, pigments, dyes, radio-opaque materials, lubricants, antioxidants, bioactive agents, antimicrobial agents, and the like, depending on the requirements and/or preferences for a particular implementation.
In a further aspect of the invention, there is provided a method for making an antithrombogenic annuloplasty ring by forming a biodegradable ring insert at least partly comprised of a material selected, for example, polyanhydrides, polyglycolides, polylactides, and polyorthoesters enclosing the ring insert within a fabric sheath. The ring insert may be formed as a solid part, may be comprised of fibrous materials, or some combination thereof, and is fabricated by any of a variety conventional techniques available for forming shaped articles from polymeric materials, including, without limitation, extrusion, molding, machining, casting, spinning, and other like processes. At some point during fabrication and/or assembly of the annuloplasty ring, or after assembly but prior to implantation, at least some portion of the ring insert and/or the fabric sheath, or some other component of the annuloplasty ring, is treated with an antithrombogenic treatment process in order to cause the incorporation of at least some antithrombogenic agent into or onto a desired portion or portions of the annuloplasty ring.